One of the great challenges in neurobiology is to understand how sensory and motor systems are integrated to produce behavior. The juxtaposition of cells with sensory and motor properties has made the superior colliculus a fruitful model for studying this process. By applying methods new to the study of the superior colliculus, including in vitro whole-cell patch-clamp recording and photostimulation, we are analyzing for the first time at the cellular level the intrinsic circuitry that links its sensory and motor functions. By filling the cells during recording with neuronal tracers and by pre-labeling them with retrogradely transported tracers, their physiology is correlated with their morphology and connections. Using this approach, we demonstrated that the superficial collicular layer, which encodes the location of visual stimuli, sends excitatory signals to a deeper layer of premotor cells, which generates commands for visually guided shifts in the direction of gaze. The premotor layer also receives a dense cholinergic input that arises from the same brainstem cells that modulate the flow of sensory information through the visual part of the thalamus to the cortex. Our first Specific Aim is to test the idea that this cholinergic input coordinates the enhancement of sensory signals transmitted to the cortex with the initiation of orienting movements toward visual stimuli. Our second Specific Aim is to test the idea that modulation of premotor activity by long-range inhibition - between the right and left colliculi and between rostral fixation and caudal gaze shifting neurons - permits the activation of premotor cells that command head and eye movements toward visual stimuli in one direction while attenuating the activity of premotor cells that would command competing movements toward stimuli in other directions. These experiments will contribute to our understanding of sensorimotor functions in the normal and diseased brain